OBJECTIVE-This study addressed the long-term effect of various diets, particularly lowcarbohydrate high-protein, on renal function on participants with or without type 2 diabetes. RESEARCH DESIGN AND METHODS-In the 2-year Dietary Intervention Randomized Controlled Trial (DIRECT), 318 participants (age, 51 years; 86%men; BMI, 31 kg/m2; mean estimated glomerular filtration rate [eGFR], 70.5mL/min/1.73m2;mean urinemicroalbumin- tocreatinine ratio, 12:12) with serum creatinine <176 μmol/L (eGFR≥30 mL/min/1.73 m2) were randomized to low-fat, Mediterranean, or low-carbohydrate diets. The 2-year compliance was 85%, and the proportion of protein intake significantly increased to 22% of energy only in the low-carbohydrate diet (P<0.05 vs. low-fat and Mediterranean). We examined changes in urinarymicroalbumin and eGFR, estimated byModification of Diet in Renal Disease and Chronic Kidney Disease Epidemiology Collaboration formulas. RESULTS-Significant (P<0.05 within groups) improvements in eGFRwere achieved in lowcarbohydrate (+5.3% [95% CI 2.1-8.5]), Mediterranean (+5.2% [3.0-7.4]), and low-fat diets (+4.0% [0.9-7.1]) with similar magnitude (P>0.05) across diet groups. The increased eGFR was at least as prominent in participants with (+6.7%) or without (+4.5%) type 2 diabetes or those with lower baseline renal function of eGFR ,60 mL/min/1.73 m2 (+7.1%) versus eGFR <60 mL/min/1.73 m2 (+3.7%). In amultivariable model adjusted for age, sex, diet group, type 2 diabetes, use of ACE inhibitors, 2-year weight loss, and change in protein intake (confounders and univariate predictors), only a decrease in fasting insulin (β = 20.211; P = 0.004) and systolic blood pressure (β = 20.25; P<0.001) were independently associated with i ncreased eGFR. Theurine microalbumin-to-creatinine ratio improved similarly across the di ets, articularly among participants with baseline sex-adjustedmicroalbu minuria,with amean change of224.8 (P<0.05). CONCLUSIONS-A low-carbohydrate diet is as safe as Mediterranean or low-fat diets in preserving/improving renal function among moderately obese participants with or without type 2 diabetes, with baseline serum creatinine <176 μmol/L. Potential improveme nt is likely to be mediated by weight loss-induced improvements in insulin sensitivity and blood pressure.